The subject matter disclosed herein relates to heterometallic compounds for treating cancers and to titanium-gold complexes in particular.
Cisplatin and its follow-on drugs (carboplatin and oxaliplatin) are used to treat 40%-80% of cancer patients, alone or in combination chemotherapy. However, the effectiveness of these drugs is still hundred by clinical problems, including acquired or intrinsic resistance, a limited spectrum of activity and high toxicity leading to side effects. Promising anticancer activities of a variety of other metal complexes have been reported in the past two decades. Metallocene dihalides (Cp2MCl2, where Cp=cyclopentadienyl, M=Ti, V, Nb, Mo or Re) were the first organometallic compounds with antitumor properties to be identified. Titanocene dichloride was the first non-platinum metal complex to enter clinical trials in 1993. Titanocene dichloride exhibited considerable antitumor activity in vitro and in vivo, even against cisplatin-resistant cells and tumor that were generally difficult to treat. Unfortunately, the efficacy of titanocene dichloride in Phase II clinical trials in patients with metastatic renal cell carcinoma or metastatic breast cancer was too low to be pursued. Alternatives to titanocene dichloride include titanocene Y and titanocene T.
Gold complexes are also a promising family of metallodrugs. In particular, a number of gold compounds have overcome cisplatin resistance to specific cancer cells. In addition, DNA is not the primary target for most gold compounds which reinforces the idea that their mode of action is different with respect to cisplatin.
Although titanium compounds and gold compounds have each received widespread attention, neither is entirely satisfactory in all situations. Improved alternatives are therefore desired. The discussion above is merely provided for general background information and is not intended to be used as an aid in determining the scope of the claimed subject matter.